A fused gene of nucleoprotein (NP) and herpes simplex virus genes (VP22) induces highly protective immunity against different subtypes of influenza virus.

We evaluated the immunogenicity and protective activity of plasmid DNA vaccines encoding the influenza virus NP gene (pNP) alone or in combination with the herpes simplex virus type 1 protein 22 gene (pVP22). Optimal immune responses were observed in BALB/c mice immunized with the combination of pVP22 plus pNP, as assessed by enzyme-linked immunosorbent assay (ELISA), enzyme-linked immunospot (ELISPOT) and intracellular cytokine staining (ICCS). These mice also showed maximal resistance following challenge with the A/PR/8/34 (H1N1) and A/Udron/72 (H3N2) strains of influenza virus. The susceptibility of immunized mice to virus infection was significantly increased following depletion of either CD4+ or CD8+ T cells. These results indicate that a plasmid DNA vaccine encoding pVP22 plus NP induces a high level of cross-protective immunity against influenza virus subtypes.